It seems that most HPLC-MS/MS methods used for quantitation of catecholamines (epinephrine, norepinephrine and dopamine, specifically) operate at low pH (commonly 3.0), and therefore demand the addition of ion pairing reagents if a C18 column is to be employed. From my understand, these conditions are used to improve catecholamine stability, and avoid formation of quinones by oxidation. Fair.
My question is; why are high pH solvents not used (> pKa + 2.0, so pH ~ 10.5), with the addition of antioxidizers, such as EDTA? I understand that this would require MS operation in negative ion mode, but should circumvent need for ion pairing reagents. Might this be possible? Has this been attempted?